Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
DNEL value:
438 mg/m³
Explanation for the modification of the dose descriptor starting point:
The test substance has a very low estimated vapour pressure and is hence not volatile. Further, the test substance synthesis and spray drying is performed in a closed process and the de-dusting agents are mixed directly with the wet press cake. Consequently, the final product consists of non-dusty granules or well dedusted powders, and the potential for the generation of inhalable forms is low. In addition, the use of this substance will not result in aerosols, particles or droplets of an inhalable size. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Hence NOAEL for oral toxicity is considered the appropriate endpoint for hazard assessment. Therefore oral absorption in rat is assumed to be 100% and inhalation absorption in humans is assumed to be 100%. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. Allometric scaling factor: 4; BW (human) = 70 kg Hrv = Human respiration rate = 10 m3 / person. Therefore, corrected NOAEC (inhalation) = 438 mg/m³ (250/4 * 70/10)
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic - for worst case
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences when calculated from human NOAEC
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral absorption in rat is 100% and dermal absorption in humans is 100% as worst case.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic - for worst case
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The test item did not show any adverse systemic or local effects either during short-term or long-term exposure. In the combined repeat-dose/developmental screening study, unspecific toxic effects have been observed in females at the highest dose tested of 1000 mg/kg body weight/day, leading to a lower litter size and litter weight in combination with a higher pup loss at birth and on Day 4 post partum. Based on the results of this study, the NOAEL for general toxicity, as well as for reproductive and developmental toxicity, was considered to be 250 mg/kg body weight/day for females and 1000 mg/kg body weight/day for males.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.65 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
DNEL value:
219 mg/m³
Explanation for the modification of the dose descriptor starting point:
The test substance has a very low estimated vapour pressure and decomposes prior to melting and is hence not volatile. Further, the test substance synthesis and spray drying is performed in a closed process and the dedusting agents are mixed directly with the wet press cake. Consequently, the final product consists of non-dusty granules or well de-dusted powders, and the potential for the generation of inhalable forms is low. In addition, the use of this substance will not result in aerosols, particles or droplets of an inhalable size. Any nuisance dust ingested will remain in the mouth/nose with the potential for subsequent oral exposure. Therefore, 100% oral absorption in rats is assumed and 100% inhalation absorption in humans is assumed. Corrected NOAEC (inhalation) = NOAEL (oral rat) / AS * BW(human) / Hrv. Allometric scaling factor: 4; BW (human) = 70 kg Hrv = Human respiration rate = 20 m3 / person. Therefore, corrected NOAEC (inhalation) = 219 mg/m3 (250/4 * 70/20)
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic - for worst case
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling done at route to route extrapolation step in accordance with left hand side of Example R. 8-2 of Appendix R. 8-2, part 1.
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor of 10 for general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral absorption in rat is 100% and dermal absorption in humans is 100% as worst case.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic - for worst case
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor of 10 for general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation not required
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic - for worst case
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for rat compared with humans is 4
AF for other interspecies differences:
1
Justification:
Allometric scaling factor considered sufficient to account for interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for the general population
AF for the quality of the whole database:
1
Justification:
GLP study conducted in accordance with OECD Guideline.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The test item did not show any adverse systemic or local effects either during short-term or long-term exposure. In the combined repeat-dose/developmental screening study, unspecific toxic effects have been observed in females at the highest dose tested of 1000 mg/kg body weight/day, leading to a lower litter size and litter weight in combination with a higher pup loss at birth and on Day 4 post partum. Based on the results of this study, the NOAEL for general toxicity, as well as for reproductive and developmental toxicity, was considered to be 250 mg/kg body weight/day for females and 1000 mg/kg body weight/day for males.